X-77830865-A-C

Position:

• chrX-77830865-A-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001367916.1(MAGT1):​c.932T>G​(p.Val311Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,157,504 control chromosomes in the GnomAD database, including 1 homozygotes. There are 395 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., 44 hem., cov: 23)
  • Exomes 𝑓: 0.0011 (1 hom. 351 hem.)
• Consequence: MAGT1 NM_001367916.1 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 8.11

Genes affected

MAGT1 (HGNC:28880): (magnesium transporter 1) This gene encodes a ubiquitously expressed magnesium cation transporter protein that localizes to the cell membrane. This protein also associates with N-oligosaccharyl transferase and therefore may have a role in N-glycosylation. Mutations in this gene cause a form of X-linked intellectual disability (XLID). This gene may have multiple in-frame translation initiation sites, one of which would encode a shorter protein with an N-terminus containing a signal peptide at amino acids 1-29. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012037069).
• BP6: Variant X-77830865-A-C is Benign according to our data. Variant chrX-77830865-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 96213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-77830865-A-C is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd4 at 44 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGT1	NM_001367916.1	c.932T>G	p.Val311Gly	missense_variant	9/10	ENST00000618282.5	NP_001354845.1
MAGT1	NM_032121.5	c.1028T>G	p.Val343Gly	missense_variant	9/10		NP_115497.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGT1	ENST00000618282.5	c.932T>G	p.Val311Gly	missense_variant	9/10	1	NM_001367916.1	ENSP00000480732	P1

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 128 AN: 110401 Hom.: 0 Cov.: 23 AF XY: 0.00133 AC XY: 44 AN XY: 33049

Gnomad AFR AF: 0.000196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000194

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00742

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.000673

GnomAD3 exomes AF: 0.00153 AC: 260 AN: 169941 Hom.: 0 AF XY: 0.00154 AC XY: 90 AN XY: 58395

Gnomad AFR exome AF: 0.000335

Gnomad AMR exome AF: 0.000246

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00922

Gnomad NFE exome AF: 0.00128

Gnomad OTH exome AF: 0.00123

GnomAD4 exome AF: 0.00108 AC: 1136 AN: 1047069 Hom.: 1 Cov.: 22 AF XY: 0.00107 AC XY: 351 AN XY: 328835

Gnomad4 AFR exome AF: 0.000160

Gnomad4 AMR exome AF: 0.000241

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00678

Gnomad4 NFE exome AF: 0.00102

Gnomad4 OTH exome AF: 0.000920

GnomAD4 genome AF: 0.00116 AC: 128 AN: 110435 Hom.: 0 Cov.: 23 AF XY: 0.00133 AC XY: 44 AN XY: 33093

Gnomad4 AFR AF: 0.000195

Gnomad4 AMR AF: 0.000194

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00742

Gnomad4 NFE AF: 0.00150

Gnomad4 OTH AF: 0.000665

Alfa AF: 0.00121 Hom.: 43

Bravo AF: 0.000676

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00179 AC: 12

ExAC AF: 0.00131 AC: 159

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia Benign:2

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 09, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 15, 2013

- -

MAGT1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 06, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia;C5231393:Congenital disorder of glycosylation, type ICC Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Pathogenic	0.46
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.30	T;T;T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.65	.;T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.012	T;T;T
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.2	.;.;M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.4	N;.;.
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	D;.;.
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.0030	.;.;B
Vest4		0.48
MVP		0.99
MPC		0.62
ClinPred		0.093	T
GERP RS		5.5
Varity_R		0.49
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs145245774; hg19: chrX-77086362;